Molecular Changes in Glutamatergic Synapses Induced by Pb 2+: Association with Deficits of LTP and Spatial Learning

Abstract

What are the molecular bases for the neurotoxicity that occurs after developmental exposure to low levels of Pb 2+, and are these effects persistent and detrimental in adults? Our inability to understand specific mechanisms behind Pb 2+ neurotoxicity has long been one of many problem areas of this preventable childhood disease. The sensitivity of the developing brain to Pb 2+-induced neurotoxicity is an outcome of the many unique characteristics that comprise the developing central nervous system. The developing brain can be exposed to significant concentrations of Pb 2+ during vulnerable periods of development such as synapse formation, gene and protein expression, and other diverse molecular changes associated with these processes. Recently, changes in NMDA receptor subunits were identified in animals that showed cognitive deficits induced by exposure to Pb 2+. This molecular association is important because it provides new evidence in the characterization of developmental Pb 2+ neurotoxicity that supports physiological findings of impairments in synaptic plasticity and behavior. This review updates information from molecular studies that can be directly associated with impairments of behavior and synaptic plasticity, and outlines the functional consequences of molecular differences in Pb 2+-exposed animals that illuminate potential mechanisms of Pb 2+-induced neurotoxicity.